Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: A longitudinal MRI study

Duygu Tosun, Norbert Schuff, Diana Truran-Sacrey, Leslie M. Shaw, John Q. Trojanowski, Paul Aisen, Ronald Peterson, Michael W. Weiner

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Aβ1-42) and elevated total tau (t-tau) and phosphorylated tau (p-tau181p) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Aβ1-42, t-tau, and p-tau181p and apolipoprotein E (ApoE) ε4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Aβ1-42 and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Aβ1-42 levels and higher tau levels supports the hypothesis that CSF Aβ1-42 and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE ε4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.

Original languageEnglish (US)
Pages (from-to)1340-1354
Number of pages15
JournalNeurobiology of aging
Volume31
Issue number8
DOIs
StatePublished - Aug 1 2010

Keywords

  • Alzheimer's disease
  • ApoE
  • Atrophy
  • Biomarkers
  • Brain tissue volume
  • Cerebrospinal fluid
  • Cortical thickness
  • Healthy aging
  • MRI
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Fingerprint Dive into the research topics of 'Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: A longitudinal MRI study'. Together they form a unique fingerprint.

  • Cite this

    Tosun, D., Schuff, N., Truran-Sacrey, D., Shaw, L. M., Trojanowski, J. Q., Aisen, P., Peterson, R., & Weiner, M. W. (2010). Relations between brain tissue loss, CSF biomarkers, and the ApoE genetic profile: A longitudinal MRI study. Neurobiology of aging, 31(8), 1340-1354. https://doi.org/10.1016/j.neurobiolaging.2010.04.030